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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Approximately a third of adults and half of children with acquired immunodeficiency syndrome (AIDS) eventually suffer from neurological manifestations, including dysfunction of cognition, movement, and sensation. Among the various pathologies reported in the brain of patients with AIDS is neuronal injury and loss. A paradox arises, however, because neurons themselves are for all intents and purposes not infected by human immunodeficiency virus type 1 (HIV-1). This paper reviews evidence suggesting that at least part of the neuronal injury observed in the brain of AIDS patients is related to excessive influx of Ca2+. There is growing support for the existence of HIV- or immune-related toxins that lead indirectly to the injury or death of neurons via a potentially complex web of interactions between macrophages (or microglia), astrocytes, and neurons. Human immunodeficiency virus-infected monocytoid cells (macrophages, microglia, or monocytes), especially after interacting with astrocytes, secrete substances that potentially contribute to neurotoxicity. Not all of these substances are yet known, but they may include eicosanoids, that is, arachidonic acid and its metabolites, as well as platelet-activating factor. Macrophages activated by HIV-1 envelope protein gp120 also appear to release arachidonic acid and its metabolites. These factors can lead to increased glutamate release or decreased glutamate reuptake. In addition, gamma interferon (IFN-gamma) stimulation of macrophages induce release of the glutamate-like agonist quinolinate. Human immunodeficiency virus-infected or gp120-stimulated macrophages also produce cytokines, including tumor necrosis factor-alpha and interleukin-1 beta, which contribute to astrogliosis. A final common pathway for neuronal susceptibility appears to be operative, similar to that observed in stroke, trauma, epilepsy, neuropathic pain, and several neurodegenerative diseases, possibly including Huntington's disease, Parkinson's disease, and amyotrophic lateral sclerosis. This mechanism involves the activation of voltage-dependent Ca2+ channels and N-methyl-D-aspartate (NMDA) receptor-operated channels, and therefore offers hope for future pharmacological intervention. This review focuses on clinically tolerated calcium channel antagonists and NMDA antagonists with the potential for trials in humans with AIDS dementia in the near future.
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PMID:AIDS-related dementia and calcium homeostasis. 784 72

The cytokines are multipotent mediators of inflammation and immunity that can affect key functions of vascular wall cells. Growing evidence suggests that cytokines participate as autocrine or paracrine mediators in atherogenesis, as cells in lesions can both produce and respond to these mediators. The functions of vascular wall cells regulated by cytokines may influence lesion initiation, progression, or complication. For example, cytokines can regulate the expression of adhesion molecules crucial to the recruitment of leukocytes to lesions, including vascular cell adhesion molecule-1 (VCAM-1). Cytokines such as interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF-alpha) can regulate the production of monocyte chemoattractant protein-1 (MCP-1), a potential signal for directed migration of monocytes into the intima. Cytokines can also regulate genes that encode other growth factors and cytokines themselves. TNF-alpha can induce IL-1 mRNA in human endothelial (EC) and smooth-muscle cells (SMC). IL-1 and TNF-alpha can augment the production by vascular cells of macrophage-colony stimulating factor (M-CSF), which may promote growth and activation of mononuclear phagocytes. Cytokines can exert both pro-and antiatherogenic actions. Activated T cells in human atheroma may secrete the lymphokine IFN-gamma, an inhibitor of SMC proliferation. Cytokines influence vasomotor tone in arteries, e.g., by inducing a form of nitric oxide synthase, the enzyme that synthesizes the vasodilatory nitric oxide radical. The cytokines also modulate endothelial functions that govern the formation and stability of blood thrombi. Finally, in the late stages of the disease, matrix metalloproteinases derived from macrophages or smooth-muscle cells themselves may contribute to weakening of the fibrous cap in the vulnerable shoulder area, promoting plaque rupture and occlusive thrombosis, culminating in the dramatic clinical manifestations of atherosclerosis, including myocardial infarction and stroke. Thus, cytokines can influence multiple aspects of atherogenesis and provide new and interesting targets for therapeutic intervention.
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PMID:Cytokines regulate vascular functions related to stability of the atherosclerotic plaque. 869 71

Nitrogen monoxide (NO) has diverse physiological roles and also contributes to the immune defense against viruses, bacteria, and other parasites. However, excess production of NO is associated with various diseases such arthritis, diabetes, stroke, septic shock, autoimmune, chronic inflammatory diseases, and atheriosclerosis. Cells respond to activating or depressing stimuli by enhancing or inhibiting the expression of the enzymatic machinery that produce NO. Thus, maintenance of a tight regulation of NO production is important for human health. Phytochemicals have been traditionally utilized in ways to treat a family of pathologies that have in common the disregulation of NO production. Here we report the scavenging activity of Pycnogenol (the polyphenols containing extract of the bark from Pinus maritima) against reactive oxygen and nitrogen species, and its effects on NO metabolism in the murine macrophages cell line RAW 264.7. Macrophages were activated by the bacterial wall components lipopolysaccharide (LPS) and interferon (IFN-gamma), which induces the expression of large amounts of the enzyme nitric oxide synthase (iNOS). Preincubation of cells with physiological concentrations of Pycnogenol significantly decreased NO generation. It was found that this effect was due to the combination of several different biological activities, i.e., its ROS and NO scavenging activity, inhibition of iNOS activity, and inhibition of iNOS-mRNA expression. These data begin to provide the basis for the conceptual understanding of the biological activity of Pycnogenol and possibly other polyphenolic compounds as therapeutic agents in various human disorders.
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PMID:Procyanidins extracted from Pinus maritima (Pycnogenol): scavengers of free radical species and modulators of nitrogen monoxide metabolism in activated murine RAW 264.7 macrophages. 962 66

Molecular studies of giant cell arteritis indicate that T cells are recruited to the wall of medium-sized and large arteries, are activated locally, produce IL-2 and IFN-gamma, and regulate the activity of tissue-infiltrating macrophages. Downstream effects of T cell activation include the production of proinflammatory cytokines, metalloproteinases, and growth factors. Growth factors are instrumental in the process of intimal hyperplasia, leading to luminal occlusion and tissue ischemia. The amounts of IL-2, IFN-gamma, and the growth factor PDGF in the vascular lesions varies among patients and are correlated with differences in patterns of clinical manifestations. Giant cell arteritis complicated by cranial ischemia, such as anterior optic neuropathy or stroke, is characterized by high levels of IFN-gamma and PDGF. If the IFN-gamma-PDGF loop is less developed, fever and wasting can dominate the disease. Dominant production of IL-2 is associated with polymyalgia rheumatica. The finding of different inflammatory pathways translating into different clinical phenotypes may reflect differences in the contribution of the arterial wall. Alternative hypotheses include a role of multiple disease-inducing antigens with different tissue distributions or tropisms.
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PMID:Giant cell arteritis--a molecular approach to the multiple facets of the syndrome. 992 95

Systemic inflammation, represented in large part by the production of pro-inflammatory cytokines, is the response of humans to the assault of the non-self on the organism. Three distinct types of human ailments - namely autoimmunity, presenile dementia (Alzheimer's disease), or atherosclerosis - are initiated or worsened by systemic inflammation. Autoimmunity is unregulated hyperimmunity to organ-specific proteins, inducing rapid turnover of antigen-specific T cells of the acquired immune system with ultimate exhaustion and loss of acquired immunity IL-2 and IFN-gamma production and proliferative decline, conforming to the limited capacity of clonal division (Hayflick phenonmenon). In Alzheimer's disease (AD), the primary degenerative process of amyloid-beta (AJ3) protein precedes a cascade of events that ultimately leads to a local "brain inflammatory response". Unregulated systemic immune processes are secondary but important as a driving-force role in AD pathogenesis. Atherosclerosis, an underlying cause of myocardial infarction, stroke, and other cardiovascular diseases, consists of focal plaques characterized by cholesterol deposition, fibrosis, and inflammation. The presence of activated T lymphocytes and macrophages indicate a local immunologic activation in the atherosclerotic plaque that may be secondary to unregulated pro-inflammatory cytokines too. The premature hyperimmunity of autoimmunity, the local "brain inflammatory response" to A/3 protein in AD, and the immune response to fatty changes in vessels in atherosclerosis all signal the critical importance of unregulated systemic inflammation to common neurological and cardiovascular disease that shortens the nominal longevity of humans.
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PMID:Unregulated inflammation shortens human functional longevity. 1113 Dec 95

Infections are a leading cause of death in stroke patients. In a mouse model of focal cerebral ischemia, we tested the hypothesis that a stroke-induced immunodeficiency increases the susceptibility to bacterial infections. 3 d after ischemia, all animals developed spontaneous septicemia and pneumonia. Stroke induced an extensive apoptotic loss of lymphocytes and a shift from T helper cell (Th)1 to Th2 cytokine production. Adoptive transfer of T and natural killer cells from wild-type mice, but not from interferon (IFN)-gamma-deficient mice, or administration of IFN-gamma at day 1 after stroke greatly decreased the bacterial burden. Importantly, the defective IFN-gamma response and the occurrence of bacterial infections were prevented by blocking the sympathetic nervous system but not the hypothalamo-pituitary-adrenal axis. Furthermore, administration of the beta-adrenoreceptor blocker propranolol drastically reduced mortality after stroke. These data suggest that a catecholamine-mediated defect in early lymphocyte activation is the key factor in the impaired antibacterial immune response after stroke.
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PMID:Stroke-induced immunodeficiency promotes spontaneous bacterial infections and is mediated by sympathetic activation reversal by poststroke T helper cell type 1-like immunostimulation. 3162 20

Vaccinations against various antigens of the central nervous system (CNS) are gaining increasing interest as a therapeutic approach in a variety of neurological diseases such as spinal cord injury, ischemic stroke, Alzheimer disease, or spongiform encephalopathy. In the present work, the time window after spinal cord injury allowing potentially therapeutic antibody to penetrate the damaged blood-brain barrier (BBB) was measured by intravenous injection of a monoclonal anti-Nogo-A antibody. Although an influx of Nogo antibodies at the lesion site was detectable up to 2 wk after injury, a significant decrease in BBB permeability was noticed within the first week. Clearly, therefore, a vaccination protocol with a rapid antibody response is required for acute therapeutic interventions after CNS trauma. We designed a conjugate vaccine paradigm with particular focus on the safety and the kinetics of the antibody response. As antigen targets, we used Nogo-A and the strongly encephalitogenic myelin-oligodendrocyte glycoprotein (MOG). Intrasplenic autoimmunization of rats with a Nogo-A-specific region fused to the Tetanus toxin C-fragment (TTC) resulted in a fast IgM response against Nogo-A. A specific switch to IgG was observed as soon as 4-7 days after intrasplenic immunization in TTC-primed animals. In spite of the induction of a specific IgG response after intrasplenic immunization, no signs of experimental autoimmune disease (EAE) or inflammatory infiltrates on histological examinations were observable. In contrast to subcutaneous immunization with MOG, in vitro cytokine secretion assays (IL-2, IL-10, and IFN-gamma) did not reveal activation of MOG-specific T cells after intrasplenic immunization. Our findings have critical implications for future strategies in the development of safe and efficient therapeutic vaccines for neurological diseases.
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PMID:Rapid induction of autoantibodies against Nogo-A and MOG in the absence of an encephalitogenic T cell response: implication for immunotherapeutic approaches in neurological diseases. 1456 89

Inflammation plays an important role in ischemic stroke and in humans IL-10 may have a beneficial effect in stroke. We mucosally administered myelin oligodendrocyte glycoprotein (MOG) 35-55 peptide to C57BL/6 mice before middle cerebral artery occlusion (MCAO) to induce an anti-inflammatory T cell response directed at CNS myelin. Nasal and oral administration of MOG(35-55) peptide decreased ischemic infarct size at 24 and 72 h after MCAO surgery. Nasal MOG(35-55) peptide was most efficacious and reduced infarct size by 70% at 24 h and by 50% at 72 h (p <or= 0.0001 vs control) and also improved behavior score. Immunohistochemistry demonstrated increased IL-10 and reduced IFN-gamma in the area surrounding the ischemic infarct following nasal treatment. Nasal MOG did not reduce infarct size in IL-10-deficient mice. Adoptive transfer of CD4(+) T cells to untreated mice from nasally tolerized mice before MCAO surgery decreased stroke size (p < 0.001 vs control), whereas, CD4(+) T cells from nasally tolerized IL-10-deficient mice had no effect. Our results demonstrate that IL-10-secreting CD4(+) T cells induced by nasal MOG reduce injury following stroke. In addition, we observed a dramatic reduction of CD11b(+) cells in nasal MOG-treated animals. CD11b(+) cells may contribute to secondary infarct expansion by enhancing NO synthesis that may be reduced by elevated IL-10 levels. Modulation of cerebral inflammation by nasal vaccination with myelin Ags that increase IL-10 in the brain may improve outcome after stroke and enhance mechanisms of recovery.
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PMID:Nasal vaccination with myelin oligodendrocyte glycoprotein reduces stroke size by inducing IL-10-producing CD4+ T cells. 1466 56

Giant cell arteritis (GCA), a vasculitis that targets medium- and large-size arteries, is ranked as a medical emergency because of its potential to cause blindness and stroke. The typical lesions, granulomas in the vessel wall, are formed by IFN-gamma-producing CD4+ T cells and macrophages. CD4+ T cells undergo in situ activation in the adventitia, where they interact with indigenous dendritic cells. Tissue injury is mediated by several distinct sets of macrophages that are committed to diverse effector functions. The dominant tissue injury in the media results from oxidative stress and leads to smooth muscle cell apoptosis and nitration of endothelial cells. Macrophage-derived growth factors are instrumental in driving the response-to-injury program of the artery that causes intimal hyperplasia and vessel occlusion. Clinical manifestations are those of tissue ischemia or a syndrome of exuberant systemic inflammation. The vascular and the systemic components of GCA contribute differentially to the disease, leading to distinct clinical phenotypes of this arteritis. Immunologically most interesting is polymyalgia rheumatica, in which the systemic component is combined with aborted vasculitis, suggesting a role for artery-specific tolerance mechanisms.
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PMID:Immunopathways in giant cell arteritis and polymyalgia rheumatica. 1487 49

Naturally occurring sexual dimorphism has been implicated in the risk, progression and recovery from numerous neurological disorders. These include head injury, multiple sclerosis (MS), stroke, and neurodegenerative diseases (Parkinson's disease (PD), Alzheimer's disease (AD) or amyotrophic lateral sclerosis (ALS). Accumulating evidence suggests that observed differences between men and women could result from estrogen's wide range of effects within the mammalian central nervous system (CNS), with it's neuroprotective effect being one of the most important. It seems possible that neuroprotective activity of estrogen could be partially a result of it's anti-inflammatory action. It has been well established that inflammation plays an important role in the etiopathogenesis and manifestation of brain pathological changes. In this regard, an important role has been suggested for pro-inflammatory cytokines produced by activated glial cells, neurons and immune cells that invade brain tissue. Within the CNS, cytokines stimulate inflammatory processes that may impair blood-brain barrier permeability as well as promote apoptosis of neurons, oligodendrocytes and induce myelin damage. Given that estrogen may modulate cytokine expression, coupled with the fact that gender differences of cytokine production are apparent in animal models of PD and MS, suggests an important connection between hormonal-cytokine link in neurodegeneration. Indeed, while MS patients and mice subjected to experimental autoimmune encephalomyelitis (EAE) display gender specific alterations of IFN-gamma and IL-12, variations of TNF and IL-6 were associated with PD. Also in case of more acute neurodegenerative conditions, such as stroke, the effect of IL-6 gene G-174C polymorphism was different in males and females. Given that our understanding of the role of estrogen on cytokine production and accompanying CNS pathological conditions is limited, the present reviews aims to present some of our recent findings in this area and further evaluate the evidence that may be relevant to the design of new hormonal anti-inflammatory treatment strategies for neurodegenerative diseases.
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PMID:Estrogen and cytokines production - the possible cause of gender differences in neurological diseases. 1577 51


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